Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene

Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorige nic, and mutations that stabilize beta-catenin are found in various human c ancers including colorectal cancer. To determine the role of stabilized bet a-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin all ele whose exon 3 was sandwiched by loxP sequences. When the germline hetero zygotes were crossed with mice expressing Cre rccombinase in the intestines , the serines and threonine encoded by exon 3 and to be phosphorylated by g lycogen synthase kinase 3 beta (GSK3 beta) were deleted in the offspring in testines, which caused adenomatous intestinal polyps resembling those in Ap C(Delta 716) knockout mice. Some nascent microadenomas were also found in t he colon. These results present experimental genetic evidence that activati on of the Wnt signaling pathway can cause intestinal and colonic tumors.